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Objective To analyze the clinical outcomes of early invasive fungal disease(IFD)in patients after allogenetic hematopoietic stem cell transplantation(allo-HCST)with metagenomic next-generation sequencing(mNGS).Methods A retrospective analysis was conducted on patients undergoing allo-HCST in our Bone Marrow Transplantation Center between July 2021 and October 2022.These patients experienced one of the following conditions within 100 d after transplantation:① Patients with persistent fever and negative blood culture after empiric antimicrobial therapy for 72 h or longer;② Hyperpyrexia of unknown origin occurred again after effective anti-infection in the past;③ Symptoms in lower respiratory tract associated with lung lesions on CT scan,and empiric anti-infective therapy was ineffective.Peripheral blood or bronchoscopic alveolar lavage fluid were tested with mNGS,and overall survival(OS)and non-relapse mortality(NRM)were analyzed.Results There were 60 patients enrolled in this study.For the peripheral blood samples of 47 cases and bronchoalveolar lavage fluid samples of 13 cases,mNGS found that 19 cases were negative to pathogens,30 cases were non-fungal positive,and 11 case were fungal positive,including 3 cases of aspergillus,5 cases of mucor,2 cases of Candida tropicalis,and 1 case of Trichosporon asahii.Of the 11 patients with fungal positive,8 achieved complete remission after antifungal therapy according to the mNGS results.The 1-year OS and NRM of the 60 patients were 70.0％(95％CI:64.1％～75.9％)and 20.0％(95％CI:11.9％～32.5％),respectively,while those of the fungal infection patients were 54.5％(95％CI:49.5％～69.5％)and 36.4％(95％ CI:15.5％～70.3％),respectively.No significant differences were seen in 1-year OS(P=0.487)and 1-year NRM(P=0.358)among the negative,fungal infection and non-fungal infection patients,neither OS(P=0.238)and NRM(P=0.154)between the fungal infection and the non-fungal infection patients.Conclusion mNGS can rapidly diagnose the early IFD after allo-HSCT,which is helpful for timely and effective treatment and improves the prognosis of patients.
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OBJECTIVE To construct a risk prediction model for non-compliance with inhaled medication in patients with chronic obstructive pulmonary disease （COPD）. METHODS A retrospective analysis was conducted on 365 COPD patients admitted to the cough and wheeze pharmaceutical care clinic of the First Hospital of Qinhuangdao from October 2021 to October 2023. The patients admitted from October 2021 to June 2023 were selected as the model group （n＝303）， and the patients admitted from July to October 2023 were selected as the validation group （n＝62）. The model group was divided into compliance subgroup （n＝126） and non-compliance subgroup （n＝177）. Univariate analysis combined with multivariate Logistic regression analysis were used to analyze the risk factors for non-compliance with inhaled formulations in patients； the risk prediction model was established through regression analysis， and the accuracy of the model prediction was evaluated based on the validation group of patients. RESULTS Multivariate Logistic regression analysis showed that simultaneous use of 2 inhaled formulations （OR＝3.730， 95%CI 1.996-6.971， P＜0.001）， the number of acute exacerbations within one year ≥2 （OR＝2.509， 95%CI 1.509-4.173， P＜0.001）， smoking （OR＝2.167， 95%CI 1.309-3.588， P＝0.003）， complicated with anxiety/depression （OR＝2.112， 95%CI 1.257-3.499， P＝0.004） and mMRC grading≥2 levels （OR＝1.701， 95%CI 1.014-2.853， P＝0.044） were risk factors for non-compliance with inhaled preparations. Based on this， a risk prediction model was established and the ROC curve was drawn. The areas under the curve of the model group and validation group were 0.836 and 0.928， and the overall accuracy of the model’s prediction was 88.71%. CONCLUSIONS The predictive model based on the simultaneous use of 2 inhaled formulations， the number of acute exacerbations within one year ≥2， smoking， complicated with anxiety/depression， mMRC grading ≥2 levels has certain predictive value for the risk of non-compliance with inhaled formulations for COPD patients.
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OBJECTIVE To construct a risk prediction model for non-compliance with inhaled medication in patients with chronic obstructive pulmonary disease （COPD）. METHODS A retrospective analysis was conducted on 365 COPD patients admitted to the cough and wheeze pharmaceutical care clinic of the First Hospital of Qinhuangdao from October 2021 to October 2023. The patients admitted from October 2021 to June 2023 were selected as the model group （n＝303）， and the patients admitted from July to October 2023 were selected as the validation group （n＝62）. The model group was divided into compliance subgroup （n＝126） and non-compliance subgroup （n＝177）. Univariate analysis combined with multivariate Logistic regression analysis were used to analyze the risk factors for non-compliance with inhaled formulations in patients； the risk prediction model was established through regression analysis， and the accuracy of the model prediction was evaluated based on the validation group of patients. RESULTS Multivariate Logistic regression analysis showed that simultaneous use of 2 inhaled formulations （OR＝3.730， 95%CI 1.996-6.971， P＜0.001）， the number of acute exacerbations within one year ≥2 （OR＝2.509， 95%CI 1.509-4.173， P＜0.001）， smoking （OR＝2.167， 95%CI 1.309-3.588， P＝0.003）， complicated with anxiety/depression （OR＝2.112， 95%CI 1.257-3.499， P＝0.004） and mMRC grading≥2 levels （OR＝1.701， 95%CI 1.014-2.853， P＝0.044） were risk factors for non-compliance with inhaled preparations. Based on this， a risk prediction model was established and the ROC curve was drawn. The areas under the curve of the model group and validation group were 0.836 and 0.928， and the overall accuracy of the model’s prediction was 88.71%. CONCLUSIONS The predictive model based on the simultaneous use of 2 inhaled formulations， the number of acute exacerbations within one year ≥2， smoking， complicated with anxiety/depression， mMRC grading ≥2 levels has certain predictive value for the risk of non-compliance with inhaled formulations for COPD patients.
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The genus Rosa (Rosaceae family) includes about 200 species spread in the world, and this genus shows unique advantages in medicine and food. To date, several scholars concentrated on compounds belonging to flavonoids, triterpenes, tannins, polysaccharide, phenolic acids, fatty acids, organic acids, carotenoids, and vitamins. Pharmacological effects such as antineoplastic and anti-cancer properties, anti-inflammatory, antioxidant, liver protection, regulate blood sugar, antimicrobial activity, antiviral activity, as well as nervous system protection and cardiovascular protection were wildly reported. This article reviews the chemical constituents, pharmacological effects, applications and safety evaluations of Rosa plants, which provides a reference for the comprehensive utilization of medicine and food resources and gives a scientific basis for the development of medicinal plants of the genus Rosa.
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Pure red cell aplasia (PRCA) is a well-recognized complication of ABO major mismatched allogeneic hematopoietic stem cell transplantation (allo-HSCT), with a reported incidence of 10%-20% (Zhidong et al., 2012; Busca et al., 2018). It is clinically characterized by anemia, reticulocytopenia, and the absence of erythroblasts in a normal-appearing bone marrow biopsy (Shahan and Hildebrandt, 2015). The mechanism for PRCA has been presumed to be persistence of recipient isoagglutinins, produced by residual host B lymphocytes or plasma cells, which can interfere with the engraftment of donor erythroid cells (Zhidong et al., 2012). Several risk factors of PRCA at presentation are known, such as presence of anti-A isoagglutinins before transplantation, reduced intensity conditioning, absence of acute graft-versus-host disease (GVHD), sibling donors, and cyclosporin A (CsA) as GVHD prophylaxis (Hirokawa et al., 2013). PRCA is not considered to be a barrier to HSCT, as some patients can recover spontaneously or benefit from various approaches including high-dose steroids, erythropoietin (EPO), plasma exchange, immunoadsorption, donor lymphocyte infusion (DLI), treatment with rituximab, bortezomib, or daratumumab, and tapering or discontinuation of immunosuppression (Hirokawa et al., 2013; Bathini et al., 2019). However, there are still some patients who fail to respond even to aggressive treatment; they become red cell transfusion-dependent and iron-overloaded, and their life quality is impaired.
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Objective@#To study the effect of WT1 expression on the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute leukemia (AL) and its significance as molecular marker to dynamically monitor minimal residual disease (MRD) .@*Methods@#Retrospectively analyzed those AL patients who underwent allo-HSCT in the First Hospital Affiliated to Zhejiang University School of Medicine during Jan 2016 to Dec 2017, a total number of 314 cases, 163 males and 151 females, median age was 30 (9-64) years old. Comparing the difference of WT1 expression at diagnosed, pre-HSCT and after HSCT. Using the receiver operating characteristic (ROC) curve to determine the WT1 threshold at different time so as to predict relapse. The threshold of WT1 expression before transplantation was 1.010%, within 3 months after HSCT was 0.079% and 6 months after HSCT was 0.375%. According to these thresholds, WT1 positive patients were divided into low expression groups and high expression groups. Analyzed the relationship between overall survival (OS) , disease-free survival (DFS) , cumulative incidence of relapse (CIR) and WT1 expression.@*Results@#The OS and DFS of high expression group pre-HSCT were lower than low expression group [69.2% (9/13) vs 89.1% (57/64) , χ2=4.086, P=0.043; 53.8% (7/13) vs 87.5% (56/64) , χ2=9.766, P=0.002], CIR was higher than low expression group [30.8% (4/13) vs 7.8% (5/64) , P=0.017]. There was no significant difference of OS and DFS between high expression and low expression group of 3 months after HSCT (P=0.558, P=0.269) . The OS and DFS of high expression group of 6 months after transplantation were both lower than low expression group (P=0.049, P=0.035) . Multivariate analysis showed that WT1>0.375% when 6 months after transplantation was the only independent prognostic factor for shorter DFS (P=0.022) . There was no statistically significant difference in CIR between the high-expression group and the low-expression group 3 months after transplantation and 6 months after transplantation (P=0.114, P=0.306) .@*Conclusion@#High expression of WT1 before and after HSCT was an adverse prognosis factor. It is of clinical practical value to use WT1 as a transplant recommendation index for patients with acute leukemia and as a marker to monitor MRD dynamically.
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The Changshu tablet [CST], one kind of Chinese patent medicine with astringent to the intestine and relieving diarrhea, was made by the root of Rose odorata Sweet var. gigantean [Coll.et Hemsl.] Rehd.et Wils. Although CST has a long history of clinical application, but the research of its chemical composition is less. So the objective of this study was to investigate the main constituents and preliminarily research its effect of the contraction of isolated intestine in vitro. The contents of total polyphenols [126.23 mg/g] and total triterpenoids [132.75mg/g] in CST were determined by ultraviolet spectrophotometry. Procyanidin B3, epigallo catechin, catechin, epicatechin, [-]-fisetinidol-[4 alpha, 8]-[-]- catechin, [4 alpha, 8]-[-]-fisetinidol-[-]-epicatechins and [+]-guibourtinidol-[4 alpha, 8]-epicatechin were identified and determined by high performance liquid chromatography and their contents were distributed from 0.04mg/g to 1.46 mg/g. CST showed significant inhibitory effect against acetylcholine-induced contraction on the rat-isolated intestinal smooth muscle with a dose-dependent manner from 0.06 to 0.6 mg/mL. The maxim inhibition rates of CST on duodenum, jejunum, ileum and colon were 65.70 +/- 3.47%, 79.74 +/- 1.27%, 58.90 +/- 1.87% and 45.75 +/- 2.21% respectively. These results indicated that CST has a spasmolytic role in gastrointestinal motility which was probably mediated through inhibition of muscarinic receptors. All these findings promote the improvement of the quality control standard of CST and provide pharmacological foundation for clinical application of CST in gastrointestinal tract
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Objective To evaluate the role of protein kinase Cα (PKCoα)/heme oxygenase-1 (HO-1) signaling pathway in lipopolysaccharide (LPS)-caused damage to type Ⅱ alveolar epithelial cells of rats and the relationship with mitochondrial fusion.Methods Type Ⅱ alveolar epithelial cells were seeded in 96-well plates at a density of 2× 105 cells/ml and divided into 5 groups (n =40 each) using a random number table method:control group (group C),Go6976 group (group G),LPS group (group L),LPS plus PKCα inhibitor Go6976 group (group LG) and LPS plus dimethyl sulfoxide (DMSO) group (group LD).Group LG and group LD were pretreated with 5 μmol/L Go6976 and the equal volume of 0.1％ DMSO,respectively,for 30 min,lipopolysaccharide (LPS) 10 μg/ml was then given to establish the model of type Ⅱ alveolar epithelial cell damage in L,LG and LD groups,Go6976 5 μmol/L was added in group G,and the equal volume of phosphate buffer solution was added in group C.The cells were collected after 24 h of incubation for measurement of malondialdehyde (MDA) and reactive oxygen species (ROS) contents,superoxide dismutase (SOD) activity and expression of PKCα,HO-1,mitochondrial fusion-related proteins 1 and 2 (Mfn1,Mfn2),optic atrophy 1 (OPA1) protein and mRNA (by fluorescent quantitative polymerase chain reaction or Western blot).Results Compared with group C,MDA and ROS contents were significantly increased,the SOD activity was decreased,the expression of PKCα and HO-1 protein and mRNA was up-regulated,and the expression of Mfn1,Mfn2 and OPA1 protein and mRNA was downregulated in L,LG and LD groups (P＜0.05),and no significant change was found in the parameters mentioned above in group G (P＞0.05).Compared with group L,MDA and ROS contents were significantly increased,the SOD activity was decreased,and the expression of PKCα,HO-1,Mfn1,Mfn2 and OPA1 protein and mRNA was down-regulated in group LG (P＜0.05),and no significant change was found in the parameters mentioned above in group LD (P＞0.05).Conclusion Activation of PKCα/HO-1 signaling pathway is the endogenous protective mechanism of LPS-caused damage to type Ⅱ alveolar epithelial cells,which may be related to promoting mitochondrial fusion in rats.
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Objective To explore the role of glucose-regulated protein 78 (GRP78),p38 mitogen-activated protein kinase(p38MAPK) signal pathway in seizure-reduced brain injures and the regulatory effect of Nimodipine on it.Methods Sprague-Dawley(SD) rats were randomly divided into status convulsion group (SC group),Nimodipine group(NM group),and a normal control group(NC group).The expressions of GRP78/Bip and p38MAPK mRNA and protein were detected by reverse transcription(RT)-PCR and immunohistochemistry.The expression of apoptosis cells was observed by TdT-mediated dUTP nick end labeling (TUNEL).Results (1) Immunohistochemistry:at 4 h after induction of status convulsion,the expression of GRP78 protein in the hippocampus CA1 domain began increasing slightly,and reached a maximum at 24 h,and then began decreasing slowly ; at 4 h after induction of status convulsion,the expression of p38MAPK protein in the hippocampus CA1 domain began increasing,and reached a maximum at 24 h,and decreased remarkably at 48 h.(2) RT-PCR:at 4 h after induction of status convulsion,the expression of GRP78 protein in the hippocampus CA1 domain began increasing slightly,and reached a maximum at 24 h,and then began decreasing slowly.The NM group was much higher than the SC group and the NC group(all P ＜ 0.05) ; at 4 h after induction of status convulsion,the expression of p38MAPK protein in the hippocampus CA1 domain began increasing,and reached a maximum at 24 h,and decreased remarkably at 48 h;the NM group was much lower than the SC group,and higher than the NC group (all P ＜ 0.05).(3) TUNEL:at 4 h after induction of status convulsion,the expression of the TUNEL positive cells in the hippocampus CA1 domain began increasing slightly,and reached a maximum at 48 h,and then began decreasing,and there was no difference between SC group and NC group;the NM group was much lower than the SC group(all P ＜ 0.05).Conclusions The correlation of the increased expression of p38MAPK and neuronal apoptosis indicates that GRP78 signal pathway may be mediated to cell apoptosis through p38MAPK.Nimodipine can affect the expression of GRP78/Bip and p38MAPK,and relieve endoplasmic reticulum stress,and lessen the pathologic damage to the hippocampus.
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Objective To discuss the possible enteric nervous pathogenesis in gastritis related GI motor disorders on the expression changes of protein gene product9. 5 in neurons from the gastric walls of gastritis rat model. Methods 35 clean grade Wister rats were randomly divided into 3 groups, which included gastritis group A (n =10), gastritis group B(n =15) and control group(n =10). Rats in gastritis group A and B received gastric perfusion of HP and the mixture of 2% aspirin and 0. 6N hydrochloric acid respectively. The control group only received gastric perfusion of saline. All of the rats were killed and the gastric mucosal tissues were obtained for the pathological and HP examination. After immunohistochemical pretreatment, the tissues were stained with PGP9. 5 and at the same time the maximum diameter (Dmax, μm), mean area(μm2) and mean optical density (nm) of the neurons from the gastric walls were compared among the groups with Image-Pro Plus professional image analysis system. Results In gastric group A, HP could be found sparsely in the mucous layer or gastric pits, and all of the rapid urease tests were positive. In the other two groups, HP could not be found, and all of the rapid urease tests were negarive. In both gastric group A and B, different grades of inflammatory cell infiltration with active inflammation signs could be found in the deep layers of mucosa, while the control group was normal. The expression mean area, mean optical density of neurons from the gastric wall of rat in group A[(77. 10 ±48. 46) μm2, (53. 25 ±41.40) nm] or B [(73. 92 ± 39. 60) μm2, (45.33 ± 33.20) nm] was obvious lower than control group [(143.51 ± 29. 84) μm2, (85. 00 ± 14. 32) nm], while there was no significant difference between gastric group A and B (P ＞0. 05) (table 1). Conclusions Hp and NSAIDs might cause gastritis and decrease the PGP9. 5 expression of Neurous from gastric walls. The decrease of PGP9. 5 expression of neurons from the gastric wall might contribute to the pathogenesis of GI motor disorders or symptoms of functional dyspepsia.
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This study was aimed at the transport across blood-brain barrier (BBB) of polysorbate-80 modified neurotoxin loaded polybutylcyanoacrylate nanoparticle (P-80-NT-NP) and its cytotoxicity. An in vitro model of BBB using rat brain microvascular endothelial cells (rBMECs) was established. The cytotoxicity of P-80-NT-NP was measured by the MTT assays, where neurotoxin (NT), nanoparticle (NP), neurotoxin nanoparticle (NT-NP) as control, and the permeability of P-80-NT-NP was determined by using of Millicell insert coculture with rBMECs and fluorescence spectrophotometry. MTT results showed that NT, NP, NT-NP and P-80-NT-NP were avirulent to rBMECs when the concentration of NT was lower than 200 ng x mL(-1). But the cytotoxicity of NP, NT-NP and P-80-NT-NP would be augmented accordingly as concentration increased (P 0.05). When the concentration of NT was 150 ng x mL(-1), the permeability on rBMECs of P-80-NT-NP and NT-NP were both significantly higher than that of NT (P < 0.01), and the permeability of P-80-NT-NP was greater than that of NT-NP (P < 0.05). In conclusion, polysorbate-80 modified neurotoxin nanoparticles can transport across the BBB, while concentration of NT is greater than 200 ng x mL(-1), P-80-NT-NP has a little cytotoxicity against rBMECs.
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Several antigen epitopes were designed according to the sequences of Swine influenza virus hemagglutinin (HA) genes and lined with the interval. The gene was amplified by PCR and sub cloned into pET30a (+) vector. The fusion protein was expressed in E. coli BL21 (DE3) by induced with IPTG and purified by affinity chromatography. The molecular weight of the protein was about 20 kD in SDS-PAGE. Immunological activity of the fusion protein was analyzed by Western blot. The results showed that the fusion protein could interact with anti-His antibody and the rabbit antiserum against SIV. The immunized mouse can produced antibodies against the target peptide and HI antibody against SIV H1N1 or H3N2. This study provides a new vaccine candidate for SIV.
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Animaux , Humains , Souris , Séquence d'acides aminés , Anticorps antiviraux , Sang , Antigènes viraux , Génétique , Allergie et immunologie , Séquence nucléotidique , Épitopes , Génétique , Allergie et immunologie , Métabolisme , Escherichia coli , Génétique , Métabolisme , Hémagglutinines , Génétique , Allergie et immunologie , Immunisation , Sous-type H1N1 du virus de la grippe A , Génétique , Allergie et immunologie , Sous-type H3N2 du virus de la grippe A , Génétique , Allergie et immunologie , Souris de lignée BALB C , Données de séquences moléculaires , Répartition aléatoire , Protéines de fusion recombinantes , Génétique , Allergie et immunologieRésumé
Objective To observe the curative effects of treatment with Edaravone for acute massive cerebral infarction.Methods 48 patients with acute massive cerebral infarction were randomized into the treatment with Edaravone group(Edaravone group,24 patients) and the conventional treatment control group(control group,24 patients).Two groups patients were admitted conventional treatment for cerebral infarction.Edaravone group patients were admitted with Edaravone 30 mg into 100 ml saline infusion introvenously,twice a day,linked 20 ～ 25 d.Respectively before and after the treatment,neurologic function dificit score(NDS),plasma fibrinogen(Fib) content,coagulation blood function,activity of superoxide dismutase(SOD) were examined.The clinical efficacy was compared between the two groups.Results NDS of tow groups after treatment were significantly lower than those of before treatment,activity of SOD were significantly increased than those before treatment(all P0.05).Significant efficiency ratio of the Edaravone group(87.5%) was significantly higher than that of the control group(45.8%)(P
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AIM:To study the telomere maintenance mechanism in mesenchymal stem calls(MSCs).METHODS:MSCs were isolated from healthy human bone marrow by their adherence to plastic and then were checked with CD14-FITC,CD45-FITC,CD44-FITC,HLA-DR-FITC,CD34-PE,CD29-PE and CD166-PE.Telomere length and ECTR DNA in MSCs were detected by Southern blotting.The localization of TRF1 and promyelocytic leukemia(PML)in MSCs were detected with immunofluorescence staining.TRAP protocol was performed to detect the telomerase activity in MSCs and MSCs-derived adipocytes.Western blotting and TRAP protocol were applied to measure telomerase activity of MSCs,which were synchronized by serum starvation and aphidicolin treatment.RESULTS:The telomere in length seemed shorter and relatively more homogeneous in MSCs and HeLa cells than that in WI-38-2RA cells.TRF1 did not concide with PML nuclear body in MSCs and HeLa cells while it exclusively did in WI-38-2RA cells.ECTR DNA was negative in MSCs and HeLa cells but positive in WI-38-2RA cells.Telomerase was negative in MSCs but it was positive in MSCs-derived adipocytes detected by TRAP.Moreover,a cell cycle-dependent expression profile of telomerase was found in MSCs when they were synchronized by serum starvation and aphidicolin treatment.Untreated MSCs expressed very low level of telomerase probed by Western blotting with 2C4 mAb,but the telomerase level had significantly increased when these cells were trapped in S phase.CONCLUSION:The telomere of MSCs is maintained by telomerase pathway instead of alternative lengthing of telomere(ALT)and the level of telomerase expression is associated with cell cycle stage.[